Autoimmune disorders in oral lichen planus: A systematic review and meta-analysis.

OBJECTIVES: The association of OLP with other autoimmune processes points to the possibility that OLP-affected patients are actually developing an autoimmune status that predisposes them to autoaggression against different targets. This systematic review and meta-analysis aim to evaluate the current evidence on the prevalence of autoimmune disorders in patients with OLP and their magnitude of association. METHODS: We searched PubMed, Embase, Web of Science, Scopus databases for the studies published before May 2021, with no limitation in regards to their publication date or language. We evaluated the quality of studies, carried out meta-analyses and performed heterogeneity, subgroups, meta-regression, and small-study effects analyses. RESULTS: Inclusion criteria were met by 153 studies (23,327 patients). Our results indicate the existence of high prevalence and a frequent association between OLP and some autoimmune disorders, especially in regards to thyroid disease (PP = 7.96%, 95% CI = 6.32-9.75; OR = 1.99, 95% CI = 1.60-2.49, p < 0.001) and diabetes mellitus (PP = 9.41%,95% CI = 8.16-10.74; OR = 1.64, 95% CI = 1.34-2.00, p < 0.001). CONCLUSIONS: Our study demonstrates the existence of a comorbidity between autoimmune thyroid diseases as well as between diabetes mellitus and OLP respectively. Quality of evidence should be upgraded on other autoimmune diseases (fibromyalgia, gastrointestinal disorders, rheumatic diseases, Sjogren's syndrome, lupus erythematosus, and dermatological diseases) for which the current data do not allow us to know whether they are really associated with OLP.

Higher daytime systolic BP, prepregnancy BMI and an elevated sFlt-1/PlGF ratio predict the development of hypertension in normotensive pregnant women.

BACKGROUND: The risk of hypertensive disorders of pregnancy (HDP) varies in women with gestational diabetes mellitus (GDM), depending on the degree of insulin resistance and is also influenced by obesity. The aim of this study was to evaluate clinical features, blood pressure (BP) profiles and inflammatory markers, to identify patients with an elevated risk of developing HDP. METHODS: A total of 146 normotensive pregnant women were studied. We analysed the relationships of BP profiles detected by ambulatory blood pressure monitoring (ABPM) with serum biomarkers and angiogenic factors and their association with the development of HDP. RESULTS: Fourteen (9.6%) women developed HDP, of which 11 had GDM and 8 had obesity. Women with HDP had higher values of 24-h and daytime systolic/diastolic BP (113/69 vs. 104/64; 115/72 vs. 106/66 mmHg, respectively; p <  0.05). Higher levels of leptin (10.97 ± 0.82 vs. 10.2 ± 1.11; p = 0.018) andmonocyte chemoattractant protein-1 (MCP-1) (5.24 ± 0.60 vs. 4.9 ± 0.55; p = 0.044) and a higher soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio (4.37 ± 2.2 vs. 2.2 ± 1.43; p = 0.003) were also observed in the HDP patients. Multivariate analysis showed that a higher sFlt-1/PlGF ratio was associated with an increased risk of developing HDP [OR = 2.02; IC 95%: 1.35-3.05]. Furthermore, higher daytime systolic BP [OR = 1.27; IC 95% 1.00-1.26] and prepregnancy body mass index (BMI) [OR = 1.14; IC 95%: 1.01-1.30] significantly increased the risk of developing HDP. CONCLUSIONS: Higher daytime systolic BP values, prepregnancy BMI and the sFlt-1/PlGF ratio are useful for identifying normotensive pregnant women with an increased risk of developing HDP.

A New Perspective on Huntington's Disease: How a Neurological Disorder Influences the Peripheral Tissues.

Huntington's disease (HD) is a neurodegenerative disorder caused by a toxic, aggregation-prone expansion of CAG repeats in the HTT gene with an age-dependent progression that leads to behavioral, cognitive and motor symptoms. Principally affecting the frontal cortex and the striatum, mHTT disrupts many cellular functions. In fact, increasing evidence shows that peripheral tissues are affected by neurodegenerative diseases. It establishes an active crosstalk between peripheral tissues and the brain in different neurodegenerative diseases. This review focuses on the current knowledge of peripheral tissue effects in HD animal and cell experimental models and identifies biomarkers and mechanisms involved or affected in the progression of the disease as new therapeutic or early diagnostic options. The particular changes in serum/plasma, blood cells such as lymphocytes, immune blood cells, the pancreas, the heart, the retina, the liver, the kidney and pericytes as a part of the blood-brain barrier are described. It is important to note that several changes in different mouse models of HD present differences between them and between the different ages analyzed. The understanding of the impact of peripheral organ inflammation in HD may open new avenues for the development of novel therapeutic targets.

Unravelling the Inflammatory Processes in the Early Stages of Diabetic Nephropathy and the Potential Effect of (Ss)-DS-ONJ.

Inflammatory processes play a central role in the pathogenesis of diabetic nephropathy (DN) in the early stages of the disease. The authors demonstrate that the glycolipid mimetic (Ss)-DS-ONJ is able to abolish inflammation via the induction of autophagy flux and provokes the inhibition of inflammasome complex in ex vivo and in vitro models, using adult kidney explants from BB rats. The contribution of (Ss)-DS-ONJ to reducing inflammatory events is mediated by the inhibition of classical stress kinase pathways and the blocking of inflammasome complex activation. The (Ss)-DS-ONJ treatment is able to inhibit the epithelial-to-mesenchymal transition (EMT) progression, but only when the IL18 levels are reduced by the treatment. These findings suggest that (Ss)-DS-ONJ could be a novel, and multifactorial treatment for DN.

Diabetes mellitus and oral cancer/oral potentially malignant disorders: A systematic review and meta-analysis.

The objective was to evaluate current evidence on the prevalence and risk of oral cancer and potentially malignant oral disorders among patients with diabetes mellitus. We searched PubMed, Embase, Web of Science, and Scopus for observational studies published before November 2019. We evaluated the study quality using GRADE, QUIPS, and a specific method for systematic reviews addressing prevalence questions. Meta-analyses were conducted, and heterogeneity and publication bias were examined. A total of 1,489 studies were found, 116 analyzed in full text, 52 included in qualitative synthesis and 49 meta-analyzed. Pooled prevalence (PP) of oral cancer in patients with diabetic was 0.25% (95% CI = 0.15-0.39)-250 per 100,000 patients with diabetes mellitus -with a greater chance of oral cancer among patients with diabetes mellitus (OR = 1.41 [95% CI = 1.10-1.81], p = .007). Patients with oral cancer and diabetes mellitus had a higher mortality than controls (HR = 2.09 [95%CI = 1.36-3.22], p = .001). Leukoplakia had a PP = 2.49% (95% CI = 1.14-4.29)-2,490 per 100,000 patients with diabetes mellitus -(OR = 4.34 [95% CI = 1.14-16.55], p = .03). A PP of 2.72 (95% CI = 1.64-4.02) was obtained for oral lichen planus among patients with diabetic -2,720 per 100,000 patients with diabetes mellitus (OR = 1.87 [95% CI = 1.37-2.57], p < .001). A low PP was estimated for erythroplakia (0.02%[95%CI = 0.00-0.12]-20 per 100,000 patients with diabetes mellitus. In conclusion, patients with diabetes mellitus have a higher prevalence and greater chance of oral cancer and OPMD development in comparison with non-diabetic patients. In addition, patients with oral cancer suffering from diabetes mellitus have a higher mortality compared to non-diabetic patients with oral cancer.

Synthesis of sp2-Iminosugar Selenoglycolipids as Multitarget Drug Candidates with Antiproliferative, Leishmanicidal and Anti-Inflammatory Properties.

sp2-Iminosugar glycolipids (sp2-IGLs) represent a consolidated family of glycoconjugate mimetics encompassing a monosaccharide-like glycone moiety with a pseudoamide-type nitrogen replacing the endocyclic oxygen atom of carbohydrates and an axially-oriented lipid chain anchored at the pseudoanomeric position. The combination of these structural features makes them promising candidates for the treatment of a variety of conditions, spanning from cancer and inflammatory disorders to parasite infections. The exacerbated anomeric effect associated to the putative sp2-hybridized N-atom imparts chemical and enzymatic stability to sp2-IGLs and warrants total α-anomeric stereoselectivity in the key glycoconjugation step. A variety of O-, N-, C- and S-pseudoglycosides, differing in glycone configurational patterns and lipid nature, have been previously prepared and evaluated. Here we expand the chemical space of sp2-IGLs by reporting the synthesis of α-d-gluco-configured analogs with a bicyclic (5N,6O-oxomethylidene)nojirimycin (ONJ) core incorporating selenium at the glycosidic position. Structure-activity relationship studies in three different scenarios, namely cancer, Leishmaniasis and inflammation, convey that the therapeutic potential of the sp2-IGLs is highly dependent, not only on the length of the lipid chain (linear aliphatic C12 vs. C8), but also on the nature of the glycosidic atom (nitrogen vs. sulfur vs. selenium). The ensemble of results highlights the α-dodecylseleno-ONJ-glycoside as a promising multitarget drug candidate.

[Family, socioeconomic status and health services: Clues to health care in diabetic patients with lower limb amputations in Andalusia. A qualitative study]. / Familia, economía y servicios sanitarios: claves de los cuidados en pacientes con diabetes y amputación de miembros inferiores. Estudio cualitativo en Andalucía.

AIM: To examine the experience of diabetic care in patients undergoing lower limb amputation. DESIGN: A qualitative study using the phenomenological approach. SETTING: Cadiz Health District. PARTICIPANTS: A total of 16 patients (11 men and 5 women) diagnosed with diabetes mellitus type 2 and with non-traumatic lower limb amputation. METHODS: Semi-structured interviews were performed, followed by a content analysis according Graneheim and Lundman. RESULTS: Four categories were identified: 1. The family is the cornerstone for diabetic care. 2. The socio-economic and working conditions determine the quality of self-care. 3. The patient-health professional interaction facilitates patient care. 4. Limitations in the provision of health services. CONCLUSION: Family, economic and working conditions, along with health system-related factors are the most important elements in the care of patients with diabetes and amputations. Social, economic and working conditions determine diabetic complications. In order to enhance health care impact on the prevention of diabetes mellitus complications, health system policy makers must take these facts seriously into consideration and in a more personalised manner.

Ghrelin mitigates ß-cell mass loss during insulitis in an animal model of autoimmune diabetes mellitus, the BioBreeding/Worcester rat.

BACKGROUND: Ghrelin is a peptide hormone with pleiotropic effects. It stimulates cell proliferation and inhibits apoptosis-mediated cell death. It prevents diabetes mellitus in several models of chemical, surgical and biological toxic insults to pancreas in both in vivo and in vitro models and promotes glucose-stimulated insulin secretion under cytotoxic conditions. It has not yet been tested in vivo in an autoimmune model of diabetes with a persistent insult to the ß-cell. Given the immunomodulating effects of ghrelin and its trophic effects on ß-cells, we hypothesized that ghrelin treatment during the early stages of insulitis would delay diabetes onset. METHODS: BioBreeding/Worcester male rats received ghrelin (10 ng/kg/day) before insulitis development. Glucose metabolism was characterized by glucose and insulin tolerance tests. ß-cell mass, islet area, islet number, ß-cell clusters, proliferation and apoptosis and degree of insulitis were analysed by histomorphometry. A Kaplan-Meier survival curve was plotted and analysed applying the log-rank (Mantel-Cox) test. RESULTS: Ghrelin treatment significantly reduced the probability of developing diabetes in our model (p < 0.0001). It decreased islet infiltration and partially prevented ß-cell mass loss, enabling the maintenance of ß-cell neogenesis and proliferation rates. Furthermore, ghrelin treatment did not induce any metabolic perturbations. CONCLUSIONS: These findings support the hypothesis that ghrelin delays the development of autoimmune diabetes by attenuating insulitis and supporting ß-cell mass. GENERAL SIGNIFICANCE: Ghrelin promotes ß-cell viability and function through diverse mechanisms that may have significant implications for diabetes prevention, therapy and also transplant success of both islets and complete pancreas. Copyright © 2016 John Wiley & Sons, Ltd.

Should the diagnostic and therapeutic protocols for adrenal incidentalomas be changed?

BACKGROUND: The prevalence of adrenal incidentalomas is increasing with the aging of the population and the use of high resolution imaging technics. Current protocols propose a comprehensive monitoring of their functional and morphological state, but with no conclusive clinical evidence that endorses it. METHOD: Retrospective study of 96 patients diagnosed with adrenal incidentaloma between 2008 and 2012. We evaluated clinical, functional and imaging at baseline and during follow-up. RESULTS: Initially, 9 cases were surgically removed: 4 due to hyperfunction (2 Cushing syndromes and 2 pheochromocytomas) and 5 due to size larger than 4cm. During follow-up one case of pheochromocytoma was diagnosed and another grew more than 1cm, needing surgery. In 98.86% of nonfunctional and benign lesions, there was no functional and/or morphological changes in the final evaluation. CONCLUSIONS: The results of our study challenge the validity of current diagnostic-therapeutic protocols of incidentalomas, which should be reassessed in prospective studies taking into account efficiency characteristics.

Glycemic variability in diagnosis of gestational diabetes as predictor of pharmacological treatment.

INTRODUCTION: To establish whether glycemic variability (GV) parameters used when gestational diabetes mellitus (GDM) has been diagnosed could help predict the probability that a patient will need pharmacological treatment, and to analyze the link of these parameters to the development of maternal-fetal complications. MATERIALS AND METHODS: A prospective study of 87 women with GDM who underwent retrospective continuous glucose monitoring (CGM) for six days between weeks 26 and 32 of gestation, following diagnosis. The mean glycemia levels and GV variables were analyzed together with their link to maternal-fetal complications, and the need for pharmacological treatment. ROC (receiver operating characteristic) curves were developed to determine validity to detect the need for pharmacological treatment. RESULTS: Patients with higher mean glycemia (p < 0.001) and continuous overlapping of net glycemic action in a period of n-hours (CONGAn) (p = 0.001) required pharmacological treatment. The ROC curves showed cut-off points of 98.81 mg/dL for mean glycemia, and 86.70 mg/dL for CONGAn, with 83.3% sensitivity and 67.8% specificity for both parameters. No relation between the GV parameters and development of maternal-fetal complications was observed. CONCLUSIONS: The use of CGM, once GDM is diagnosed, enables us to identify those patients who would benefit from closer monitoring during gestation, and facilitate a speedier take-up of pharmacological treatment. However, prospective studies involving a higher number of patients are needed, as well as a cost assessment for recommending the use of CGM following GDM diagnosis.

Nitric oxide is a mediator of antiproliferative effects induced by proinflammatory cytokines on pancreatic beta cells.

Nitric oxide (NO) is involved in several biological processes. In type 1 diabetes mellitus (T1DM), proinflammatory cytokines activate an inducible isoform of NOS (iNOS) in ß cells, thus increasing NO levels and inducing apoptosis. The aim of the current study is to determine the role of NO (1) in the antiproliferative effect of proinflammatory cytokines IL-1 ß , IFN- γ , and TNF- α on cultured islet ß cells and (2) during the insulitis stage prior to diabetes onset using the Biobreeding (BB) rat strain as T1DM model. Our results indicate that NO donors exert an antiproliferative effect on ß cell obtained from cultured pancreatic islets, similar to that induced by proinflammatory cytokines. This cytokine-induced antiproliferative effect can be reversed by L-NMMA, a general NOS inhibitor, and is independent of guanylate cyclase pathway. Assays using NOS isoform specific inhibitors suggest that the NO implicated in the antiproliferative effect of proinflammatory cytokines is produced by inducible NOS, although not in an exclusive way. In BB rats, early treatment with L-NMMA improves the initial stage of insulitis. We conclude that NO is an important mediator of antiproliferative effect induced by proinflammatory cytokines on cultured ß cell and is implicated in ß -cell proliferation impairment observed early from initial stage of insulitis.

Significance of Umbilical Cord Leptin Profile during Pregnancy in Gestational Diabetes Mellitus-A Systematic Review and Meta-Analysis.

BACKGROUND: The literature provides limited evidence of cord blood leptin levels in gestational diabetes mellitus (GDM), with contradictory and inconsistent results with respect to their possible implications for maternal, perinatal, and future complications. METHODS: MEDLINE/PubMed, Embase, Scopus, and Web of Science databases were searched in order to investigate the state of evidence on the association of leptin profile in cord blood during perinatal complications in GDM. We critically assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analyses were performed, and heterogeneity and publication bias were analyzed. RESULTS: sixteen primary-level studies were included, recruiting 573 GDM and 1118 control pregnant women. Cord blood leptin levels were significantly higher in GDM participants compared to controls (standardized mean difference [SMD] = 0.59, 95% confidence intervals (CI) = 0.37 to 0.80, p < 0.001). All subgroups also maintained significant differences stratified by continents (Asia: SMD = 0.91, 95% CI = 0.45 to 1.37, p < 0.001; Europe: SMD = 0.38, 95% CI = 0.20 to 0.56, p < 0.001), analysis technique (ELISA: SMD = 0.70, 95% CI = 0.44 to 0.97, p < 0.001; RIA: SMD = 0.30, 95% CI = 0.11 to 0.49, p = 0.002), and sample source (plasma: SMD = 0.71, 95% CI = 0.33 to 1.09, p < 0.001; serum: SMD = 0.55, 95% CI = 0.34 to 0.77, p < 0.001). CONCLUSION: Cord blood leptin levels were significantly higher in GDM compared to controls. Further research is needed to clarify its role as a predictive biomarker of subsequent metabolic diseases in mothers with GDM and offspring.

Significance of cell adhesion molecules profile during pregnancy in gestational diabetes mellitus. A systematic review and meta-analysis.

Endothelial dysfunction has been considered as a key etiological factor contributed to the development of vascular disease in diabetes mellitus. Serum level of endothelial cell adhesion molecules (AMs) were reported to be increased in GDM and pregnant women with normal glucose tolerance when compared with nonpregnant women. The literature provides limited evidence of endothelial dysfunction in GDM with heterogeneous and contradictory results respect to their possible involvement in maternal, perinatal and future complications. Our objective is to evaluate current evidence on the role of AMs in maternal and perinatal complications in women with GDM. PubMed, Embase, Web of Science, and Scopus databases were searched. We evaluated the studies' quality using the Newcastle-Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Nineteen relevant studies were finally included, recruiting 765 GDM and 2368 control pregnant women. AMs levels were generally higher in GDM participants showing statistical significance maternal ICAM-1 levels (SMD = 0.58, 95% CI = 0.25 to 0.91; p = 0.001). Our meta-analysis did not detect significant differences in subgroups or in meta-regression analyses. Future studies are needed to establish the potential role of these biomarkers in GDM and its complications.

Cardiovascular Risk Factors in Transgender People after Gender-Affirming Hormone Therapy.

INTRODUCTION: In the last decade, healthcare for the transgender population has increased considerably in many countries thanks to depathologization movements and the easier accessibility of medical assistance. The age at which they request to start gender-affirming hormones (GAHs) is increasingly younger. The cardiovascular risk associated with hormonal treatment is a novel research field, and the published studies are heterogeneous and inconclusive. Our objective is to determine the metabolic impact of GAHs in the transgender people treated in our Gender Identity Treatment Unit. METHODS: We designed a pre-post study to analyze changes in anthropometric parameters (weight and body mass index), analytical determinations (fasting blood glucose, glycated hemoglobin, and lipoproteins), and blood pressure control in the transgender population treated with GAHs in Puerta del Mar University Hospital. These variables were collected before and one year after hormonal therapy. RESULTS: A total of 227 transgender people were recruited between 2017 and 2020, 97 (40.09%) transwomen and 136 (59.91%) transmen. The average age at which GAHs began was 18 years. Weight, body mass index, and blood pressure increased significantly in both genders. Transmen showed a more atherogenic lipid profile, with a decrease in cholesterol LDL (p < 0.001) and an increase in triglycerides (p < 0.001). The risk of developing prediabetes or diabetes did not increase one year after treatment, although non-specific alterations in carbohydrate metabolism were detected, such as an increase in glycated hemoglobin in transmen (p = 0.040) and fasting blood glucose in transwomen (p = 0.008). No thromboembolic processes or cardiovascular events were reported during the first year of treatment. CONCLUSION: In our setting, transgender people developed changes in their metabolic profiles in the first year after hormonal treatment. Both transmen and transwomen showed early alterations in lipid and carbohydrate metabolism, slight elevations in blood pressure, and a tendency to gain weight. This makes lifestyle interventions necessary from the beginning of GAHs.

Adipokines and metabolic syndrome risk factors in women with previous gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) has been recognized as a significant risk factor for metabolic syndrome and CVD. The aim of the study was to evaluate the relationships between levels of cytokines, components of metabolic syndrome and cardiovascular risk markers in women with previous gestational diabetes. METHODS: Women (n = 41) with gestational diabetes background (cases) and 21 healthy women (controls) in the postpartum period were enrolled. Demographic and clinical data, lipid and carbohydrate metabolism and uric acid and adipokine levels (TNF-α, IL-6, leptin and adiponectin) were compared and their relationships analysed. Metabolic syndrome prevalence was calculated by WHO and NCEP-ATPIII definitions. RESULTS: There were significant differences between cases and controls: body mass index (kg/m(2) ) 27.4 ± 5.6 vs 23.9 ± 3.6 (p = 0.013), waist circumference (cm) 85.2 ± 12.9 vs 77.5 ± 9.0 (p = 0.017), metabolic syndrome (WHO definition) 14.6% vs 0% (p = 0.012), metabolic syndrome (NCEP-ATPIII definition) 22% vs 0% (p = 0.002), low HDL 36.6% vs 9.5% (p = 0.024), fasting glucose (mmol/L) 5.4 ± 0.6 vs 4.9 ± 0.2 (p < 0.001), glucose 120' oral glucose tolerance test (mmol/L) 5.8 ± 1.7vs 4.7 ± 0.8 (p = 0.007), fasting insulin (µU/mL) 13.4 ± 8.1 vs 8.4 ± 4.3 (p = 0.004), HOMA index 3.3 ± 2.3 vs 1.8 ± 1.0 (p = 0.002), HbA(1c) (%) 5.4 ± 0.2 vs 5.2 ± 0.2 (p = 0.021), uric acid (mg/dL) 4.1 ± 1 vs 3.5 ± 0.6 (p = 0.009), leptin (ng/mL) 32 025.5 ± 19 917.3 vs 20 258.9 ± 16 359.9 (p = 0.023), respectively. CONCLUSIONS: Women with previous gestational diabetes have central adiposity, atherogenic lipid profile, carbohydrate intolerance and adverse adipokine profile, all of which are risk factors for the future development of metabolic disease and CVD.

Special Issue "The Prevention, Treatment, and Complications of Diabetes Mellitus".

Diabetes mellitus (DM) is a world health problem of global repercussion [...].

Significance of Serum-Plasma Leptin Profile during Pregnancy in Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Gestational diabetes mellitus (GDM) represents a stage of subclinical inflammation and a risk factor for subsequent future type 2 diabetes and cardiovascular disease development. Leptin has been related with vascular and metabolic changes in GDM with heterogeneous and contradictory results with respect to their possible involvement in maternal, perinatal, and future complications. Our objective is to evaluate current evidence on the role of leptin in maternal and perinatal complications in women with GDM. PubMed, Embase, Web of Science, and Scopus databases were searched. We evaluated the studies' quality using the Newcastle-Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Thirty-nine relevant studies were finally included, recruiting 2255 GDM and 3846 control pregnant women. Leptin levels were significantly higher in GDM participants than in controls (SMD = 0.57, 95%CI = 0.19 to 0.94; p < 0.001). Subgroup meta-analysis did not evidence significant differences in leptin in the different trimesters of pregnancy. Meta-regression showed a positive significant relationship for HOMA in the GDM group (p = 0.05). According to these results, it seems that high levels of leptin can be used as predictive markers in GDM.

IL-1ß Implications in Type 1 Diabetes Mellitus Progression: Systematic Review and Meta-Analysis.

During Type 1 Diabetes Mellitus (T1DM) progression, there is chronic and low-grade inflammation that could be related to the evolution of the disease. We carried out a systematic review and meta-analysis to evaluate whether peripheral levels of pro-inflammatory markers such as interleukin-1 beta (IL-1ß) is significantly different among patients with or without T1DM, in gender, management of the T1DM, detection in several biological fluids, study design, age range, and glycated hemoglobin. We searched PubMed, Embase, Web of Science, and Scopus databases, and 26 relevant studies (2186 with T1DM, 2047 controls) were included. We evaluated the studies' quality using the Newcastle−Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Compared with controls, IL-1ß determined by immunoassays (pooled standardized mean difference (SMD): 2.45, 95% CI = 1.73 to 3.17; p < 0.001) was significantly elevated in T1DM. The compared IL-1ß levels in patients <18 years (SMD = 2.81, 95% CI = 1.88−3.74) was significantly elevated. The hemoglobin-glycated (Hbg) levels in patients <18 years were compared (Hbg > 7: SMD = 5.43, 95% CI = 3.31−7.56; p = 0.001). Compared with the study design, IL-1ß evaluated by ELISA (pooled SMD = 3.29, 95% CI = 2.27 to 4.30, p < 0.001) was significantly elevated in T1DM patients. IL-1ß remained significantly higher in patients with a worse management of T1DM and in the early stage of T1DM. IL-1ß levels determine the inflammatory environment during T1DM.

Adult kidney explants is a physiologic model for studying diabetic nephropathy.

Inflammatory processes play a central role in the pathogenesis of diabetic nephropathy (DN) in the early stages of the disease. In vitro approach using cell lines help to understand the mechanisms involves and allow the molecular and biochemical processes. Adult kidney (AK) explants remain an essential instrument for advancing our understanding of the molecular and cellular regulation of signalling pathways from an organotipic view with physiological system interaction integrated. AK explants from T1DM animal model (BB rat) are obtained by slicing central kidney area preserving the organ's cytoarchitecture and reproduce the classical events detected during the DN in an in vivo model such as inflammation, epithelial-mesenchymal transition (EMT) processes by the modulation of a-SMA and e-Cadherin among others which have been determined by qRT-PCR, western-blot and immunohistochemistry. In this regard, AK explants reproduce the signalling pathways involve in DN progression (proinflammatory NFkB and inflammasome complex). This work demonstrates AK explants is a physiological experimental approach for studying the development and progression of DN. Furthermore, the inflammatory processes in AK explants under a diabetic environment and/or BB rats could be modulated by potential treatments for DN.

Proinflammatory Polyphosphate Increases in Plasma of Obese Children with Insulin Resistance and Adults with Severe Type 2 Diabetes.

Obesity increases the risk of insulin resistance and type 2 diabetes through increased inflammation at cellular and tissue levels. Therefore, study of the molecular elements involved in obesity-related inflammation may contribute to preventing and controlling it. Inorganic polyphosphate is a natural phosphate polymer that has recently been attracting more attention for its role in inflammation and hemostasis processes. Polyphosphates are one of the main constituents of human platelets, which are secreted after platelet activation. Among other roles, they interact with multiple proteins of the coagulation cascade, trigger bradykinin release, and inhibit the complement system. Despite its importance, determinations of polyphosphate levels in blood plasma had been elusive until recently, when we developed a method to detect these levels precisely. Here, we perform cross sectional studies to evaluate plasma polyphosphate in: 25 children, most of them with obesity and overweight, and 20 adults, half of them with severe type 2 diabetes. Our results show that polyphosphate increases, in a significant manner, in children with insulin resistance and in type 2 diabetes patients. As we demonstrated before that polyphosphate decreases in healthy overweight individuals, these results suggest that this polymer could be an inflammation biomarker in the metabolic disease onset before diabetes.